ABSTRACT Nearly 1.3 million cesareans are performed each year, resulting in the birth of one third of all children nationwide. When indicated, cesarean sections reduce morbidity and mortality to mother and fetus. However, many cesareans do not have a clear medical indication leading to an increase in serious maternal and perinatal morbidity and mortality. Increasing evidence also suggests that risks to offspring may extend to chronic-non communicable conditions. Consistent evidence shows that individuals born by cesarean are at an increased risk of obesity as children and that higher rates of obesity persist through adult life, raising the possibility that the long-term health consequences of being born by cesarean may extend to an increased risk of obesity-related chronic conditions including common cancers (breast, prostate, colorectal), cardiovascular disease and type 2 diabetes. However, data on the association of birth by cesarean with risk factors for or biomarkers of chronic disease risk remains scarce. There is also a paucity of information regarding the biologic mechanisms underlying the relation between cesarean delivery and offspring chronic disease risk. This proposal addresses these knowledge gaps. Specifically, we propose to evaluate the relation of birth by cesarean with pubertal onset ?an established risk factor for breast cancer; with longitudinal trajectories in biomarkers of chronic disease risk ?including markers of mitogenesis, inflammation, insulin resistance, lipid metabolism and adipose tissue activity; and with longitudinal trajectories in body composition (Aims 1 and 2). In addition, we propose to evaluate the relation of birth by cesarean section with longitudinal trajectories in whole genome DNA methylation patterns and gut microbiome (Aims 3 and 4) in order to gain further understanding on the biological underpinnings of the long-term health consequences of birth by cesarean.